Though healthy newborn infants do not bleed despite low levels of blood coagulation factor activities, hemorrhage or thrombosis is found in 40% of neonatal deaths and is associated with prematurity, hypoxemia, acidosis, blood loss, and hypotension. There is little information on the development of hemostasis in the fetus. The chronically catheterized fetal lamb model will also serial study of normal hemostasis throughout the third trimester of gestation. It is a model for study of the effects of individual and combined stresses such as acidosis, hypothension, blood loss, and hypoxia on this developing system. It can also be used or adopted for examining the effects of hormonal changes such as cortisol, thyroxin, and insulin. Measurement of coagulation factors, fibrinolytic activities, and vascular endothelial release of important mediaters are necessary to evaluate hemostasis. This project proposed such measures in chronically catheterized fetal lambs. The fetuses will be exposed to common physiologic stresses such as hypotension with and without acidosis, blood loss, and hyperinsulinemia. The studies will complement our previous experiments on the effects of hypoxemia, acidosis, glucocorticoids, and thyroxin on fetal hemostasis. Having defined the responses of fetal hemostatis to the physiologic stresses and hormonal changes commonly experienced in premature infants, studies of prematurely delivered fetuses will be conducted. These studies will determine which stresses are important in the development of hemostatic disorders found in premature infants, and indicate therapeutic modalities to be tested for their effectiveness in preventing these hemorrhagic and thrombotic complications. The studies will provide needed information on the development of hemostasis in the fetus, the causes of disorders of hemostasis in the neonate, and lead to improved therapeutic measures to prevent hemorrhage and thrombosis.